tbuckley/cabot-search huggingface dataset:
Association of enrollment duration on trial outcome in phase 3 randomized controlled trials: A pancancer analysis spanning 67 years.
Authors: Xuanyi Li, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2022)

e13597 Background: Randomized controlled trials (RCTs) inform the standard of care in clinical oncology, yet a substantial proportion yield negative results. Difficulty with patient enrollment is a problem commonly encountered in the conduct of large multicenter RCTs, leading to slow enrollment. Slow enrollment can lead to increased financial costs, delayed reporting, and decreased relevance of trial results if standards of care shift. The effects of slow enrollment on trial success are understudied. We hypothesized that longer enrollment periods would be inversely correlated with trial success, after adjustment for year of study. Methods: Phase 3 RCTs studying malignant hematologic and solid tumor conditions available on the HemOnc.org website through December 31, 2021, were included in the analysis. HemOnc.org contains nearly all phase 3 RCTs of systemic anticancer therapy registered on ClinicalTrials.gov (with results) or with publications indexed in PubMed. Start year and end year of enrollment and comparative efficacy of control and experimental arms of RCTs were extracted. RCTs were deemed positive if the experimental arms were superior in superiority trials or non-inferior in non-inferiority trials, or if control arms were inferior in superiority trials. The remaining RCTs were deemed negative. Logistic regression was used to analyze the relationship between length of enrollment period and trial outcome, adjusted for year of study enrollment start. Results: The analysis included 3072 phase 3 RCTs spanning 99 different cancer types, enrolling from 1955-2019. Breast cancer was the most studied condition (n=554 trials) followed by non-small cell lung cancer (n=314 trials). 1513 (49.2%) of RCTs reported positive trial outcomes. The overall median enrollment period was 4 years (range 1-16 years). Negative trials took 1 year longer, on average, to complete enrollment (Table). The logistic regression model showed that shorter enrollment periods were associated with trial success. Later enrollment start year was also independently associated with trial success (Table). Conclusions: Our study showed that shorter enrollment period was significantly associated with positive trial outcomes. The success rate of trials has also increased over time; this could reflect both more efficacious drugs as well as more conservative enrollment criteria. Our main limitation is that we do not have data on early termination or closure for futility; these two issues might arise in both fast and slow accruing studies, which would bias results towards the null. The results of this analysis emphasize the importance of rapid phase 3 trial enrollment.[Table: see text]
High SARS-CoV-2 seroprevalence in HIV patients originating from sub-Saharan Africa in the Ile-de-France area
Authors: Basma ABDI, Aude Laetitia NDOADOUMGUE, Siham DJEBARA, Karen ZAFILAZA, Romain PALICH, Stéphane MAROT, Luminata SCHNEIDER, Marc WIRDEN, Sophie SEANG, Yasmine DUDOIT, Elisa TEYSSOU, Roland TUBIANA, Cathia SOULIE, Marc Antoine VALANTIN, Christine KATLAMA, Vincent CALVEZ, Lambert ASSOUMOU, Anne-Geneviève MARCELIN, Valérie POURCHER
Journal: Journal of Infection (2022)
Ancestry-specific risk of triple-negative breast cancer (TNBC) associated with germline pathogenic variants (PV) in hereditary cancer (CA) predisposition genes.
Authors: Michael J. Hall, Elisha Hughes, Matthew Kucera, John Kidd, Ryan Bernhisel, B Hullinger, Thomas Paul Slavin, Allison W. Kurian
Journal: Journal of Clinical Oncology (2022)

10517 Background: TNBC represents ̃15% of invasive BC. Ancestry-specific variabilities in TNBC risk are well-described, with African American (AA) women experiencing higher incidence and mortality from TNBC than women of other races/ethnicities. Increased risk of TNBC has been associated with both rarer (e.g. RAD51C/D, BARD1) and more commonly detected (e.g. BRCA1/2, PALB2) germline PV in hereditary CA predisposition genes, but less is known about ancestry-specific TNBC risks for PV carriers. Methods: We examined clinical and genetic records from women referred for multigene CA panel testing (9/2013-5/2020). Multivariable logistic regression was used to test associations of PV in 13 genes with risk of TNBC after accounting for age, ancestry, and personal/family CA history. We analyzed each gene in the full cohort, and in subcohorts defined by self-reported ancestry. Effect sizes are expressed as odds ratios with 95% confidence intervals. Seven genes are not reported in ancestry-stratified analyses due to small numbers of PV carriers with TNBC. Results: From 627,219 individuals referred for multigene panel testing, 115,337 (18.4%) women with personal history of BC were identified, of whom 17,951 (15.6%) reported TNBC. Personal history of TNBC was reported more frequently in women of African ancestry (26.9%) than in women of European (13.9%) or Asian (11.7%) or Latinx ancestry (14.9%). Ancestry-stratified risks of TNBC associated with germline PVs are seen in the Table. Conclusions: While small samples sizes limit some gene-specific analyses, comparable ancestry-specific risks of TNBC were seen across the racial/ethnic groups examined here. [Table: see text]
Assessing feasibility and utility of an implicit bias training program for addressing disparities in cancer clinical trial participation.
Authors: Nadine Barrett, Leigh Boehmer, Janelle Schrag, Al Bowen Benson, Sybil Green, Leila Hamroun, Alexandra Howson, Khalid Matin, Randall A. Oyer, Lori J. Pierce, Sanford Earl Jeames, Karen Marie Winkfield, Eddy Shih-Hsin Yang, Victoria Zwicker, Suanna Steeby Bruinooge, Patricia A. Hurley, Jen Hanley Hanley Williams, Carmen Guerra
Journal: Journal of Clinical Oncology (2022)

e18599 Background: Low participation of Black, Hispanic, Latinx and other underrepresented racial/ethnic groups in clinical research remains a problem across the U.S. Recent studies have highlighted that stereotypes, assumptions, and bias play a role in lack of diversity in cancer trial participation. To help address this, the Association of Community Cancer Centers (ACCC) and American Society of Clinical Oncology (ASCO) piloted an implicit bias training program for clinical research teams. Methods: Adapted from the Duke University Just Ask™ program, the pilot program is comprised of eLearning modules which can be completed in about 60 minutes. Features include education on diversity, equity, and bias in clinical trial participation, case vignettes, and strategies to mitigate disparities. A call was issued to members of both organizations. After completing the training, all individual participants were asked to complete a retrospective pre/post survey to assess change in knowledge and attitude. Focus groups explored participants’ experience with the training. Another survey was administered 6 weeks later to assess sustainability of changes. Results: Research teams from 50 programs were selected for the pilot. 129 individuals consented, and 126 completed the training and evaluations (98% response rate). 48% of participants reported that they had completed training on implicit bias and/or related topics prior to the pilot. Increased levels of knowledge were reported across all key training concepts, with an average % increase from 19% to 45%. Similar increases were observed for strategies for addressing implicit bias, with an average % increase from 10% to 31%. At 6 weeks post-training, there was a slight decrease in knowledge across most items, from -1% to -8%. Most (92%) participants reported satisfaction with the course, and most (92%) indicated they would recommend it to a colleague and would recommend implementing it at their program. Suggestions to improve the course included streamlining content and providing additional tools and resources. Conclusions: Pilot findings support the feasibility and utility of the training, which can help cancer programs to address disparities in clinical research. Next steps include modifying the course based on participant feedback, disseminating the training and supplementary resources, and exploring options for assessing the impact on upstream outcomes such as diversity in trial participation.[Table: see text]
Specific and common molecular alterations in knock outs of 3 desmosomal genes in HL1 cell model of Arrhythmogenic Cardiomyophathy
Authors: M Vallverdu-Prats, R Brugada, M Alcalde
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Obra Social “La Caixa Foundation” Introduction Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a heritable cardiac disease characterized by a progressive loss of myocardium and its replacement by fibrofatty tissue that predominantly affects the right ventricle (1,2). Worldwide prevalence of ARVC is ranging from 1:1000 to 1:5000 (3,4), and it is responsible for around 20% of all cases of sudden cardiac death (SCD) among people under 35 years of age (5). The main genetic cause are mutations in desmosomal genes (4). It is known that mutations in those genes could alter important molecular functions such as calcium homeostasis (6), and they also could cause important structural and electrical alterations such as fibrosis, adipogenesis, inflammation and arrhythmogenesis (7). We lack better understanding of those pathophysiological mechanisms and their relationship with the causal gene. Purpose This study aims to elucidate molecular pathways triggered by genetic defects in three of the main genes in ARVC and determine common and gene-specific molecular features. Methods Cardiac HL-1 cell line was edited by CRISPR/Cas9 to generate Knock Outs (KO) of three of the most frequent causal genes in ARVC: PKP2, DSG2 and DSC2. Expression levels of ARVC-related genes were tested by RT-PCR: desmosome, calcium handling and connexome related genes. Changes in the total amount of protein were checked by western blot using total protein lysate. Moreover, calcium transients were performed on all clones. Results HL1 KO-PKP2 showed downregulation of SCN5A, CX43, RyR2, Atp2a2, Slc8a1, Casq2, ANK2, DSC2 DSG2 and DSP. HL1 KO-DSG2 showed a downregulation of ANK2, DSC2, CX43 and PG and HL1 KO-DSC2 clones presented a downregulation of CASQ2 and ANK2. Functionally, calcium transients showed significant differences in 10mM peak of caffeine in PKP2 but still not conclusive for DSC2 and DSG2 clones. Conclusions Results suggest that pathophysiological mechanisms of ARVC are partially depending on the causal gene. Loss of function of PKP2 and DSC2 may be related to a dysregulation of calcium homeostasis and loss of function of DSG2 may cause alterations in connexome genes expression related to electrical dysfunction. Moreover, the absence of ANK2 expression in all HL1 cell lines might suggest a common molecular hallmark of ARVC in the presented cell model.
Outcomes Among Patients With 1-Year Survival After Intensive Care Unit Treatment for COVID-19—Reply
Authors: Hidde Heesakkers, Mark van den Boogaard, Marieke Zegers
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
DIPG-56. Development and application of a novel antibody against CD99 as a therapeutic strategy in Diffuse Midline Glioma
Authors: Sujatha Venkataraman, Ilango Balakrishnan, krishna Madhavan, Senthilnath Lakshmana Chetty, Angela Pierce, Susan Fosmire, Zachary Nuss, Philip Coleman, Adam Green, Rajeev Vibhakar
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: There is an unmet need to identify novel targeted therapies for Diffuse Midline glioma (DMG) which is currently a refractory disease. Recently, we identified high expression of a cell surface antigen, CD99 in H3K27M-mutant expressing DMGs compared to other normal brain counterparts. We developed a novel chimeric CD99 antibody and tested the anti-tumor efficacy of this antibody in vitro and in vivo. METHOD: Bio-legend cell-surface screening was performed in H3K27M-mutant and WT DMG cells. Functional role of CD99 was studied using CD99 proficient and depleted tumors. Designed and synthesized CD99 antibody with a new binding sequence on a human IgG scaffold and performed cell toxicity and growth-inhibitory studies using DMG tumor and normal cells. We also performed these studies in combination with radiation. Multiple patient-derived orthotopic DMG xenograft models was used to test the antibody efficacy. Different antibody delivery routes, that are clinically relevant were investigated. RESULTS: CD99 expression is transcriptionally regulated by H3K27M and is enriched on the cell surface of K27M tumors compared to WT DMG tumors. Our new CD99 antibody (10D1 clone) significantly reduced DIPG tumor cell proliferation in vitro. Intravenous infusion of this antibody in DIPG tumor bearing mice showed complete clearance of tumor that prolonged animal survival suggesting the enhanced anti-tumor efficacy of 10D1-CD99 and importantly, its ability in crossing the blood-brain-barrier and reaching the pons target site. Loco-regional administration of 10D1 showed similar anti-tumor effects even at much reduced antibody concentrations while toxicity to CD99-expressing T cells was minimum. Radiation increased CD99 expression and enhanced the cytotoxic effect of 10D1-CD99. CONCLUSION: We have developed a novel CNS penetrant CD99 antibody that is an attractive therapeutic strategy in treating DMG. 10D1 is currently in development as a therapeutic.
Outcomes Among Patients With 1-Year Survival After Intensive Care Unit Treatment for COVID-19
Authors: Nicola Latronico, Frank A. Rasulo, Simone Piva
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Signatures of positive selection are enriched in genome‐wide associated allergy alleles
Authors: Jingyun Li, Xu Zhang, Yunbo Gao, Jian Jiao, Chengshuo Wang, Yuan Zhang, Luo Zhang
Journal: Allergy (2022)

Appendix S1 Table S1-S3 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The future of the oncology workforce: Presenters at an international trainee oncology conference.
Authors: Andrea Anampa-Guzmán, Silvana Lucero Loli Guevara, Luis Enrique Nimboma Sanchez, Cristian Antonio Gutierrez-Narvaez, Roberto Antonio Leon-Ferre
Journal: Journal of Clinical Oncology (2022)

11035 Background: In 2017, ASCO established the ASCO medical student and resident Abstract Forum. This study aimed to describe the characteristics of the ASCO medical student and resident abstract forum participants. Methods: We conducted a retrospective, observational study of Abstract Forum participants from 2017 to 2021. Descriptive statistics were used to summarize the participants' demographics by gender, stage of training, and institution location. We reported the publication rates and career paths of presenters. Results: The number of participants has more than tripled in the five years since the program's inception. Female participants are almost half of the total. In 2017, there was only one international participant. Over the subsequent five years, international members have steadily increased and represented nearly one-third of all participants in 2021. In the inaugural year, most forum participants were from institutions with ASCO Sponsored Oncology Student Interest Groups (OSIG), but in 2021 almost half were from institutions without OSIGs. The majority of participants were medical students, followed by internal medicine residents. Of a total of 179 abstracts presented between 2017 and 2021, 35 (19.55%) were subsequently published as full-text peer-reviewed manuscripts. Studies presented orally and studies presented by participants from the United States were significantly more frequently published as articles. 58.49% of medical student presenters that started residency chose Internal Medicine or Radiation Oncology. 50% of the student presenters that graduated internal medicine residency went to Hematology-Oncology fellowship. Most of the resident presenters that completed residency went to pursue careers in Hematology-Oncology (72.73%). Conclusions: The steady increase in participants since the program's creation demonstrates interest in the medical student and internal medicine resident community in these types of initiatives. The increase in international participants over the years highlights opportunities for ASCO to expand its global reach and efforts, particularly in low-income countries where trainees have the highest need for mentoring and organized support. Our study provides critical insights into the profile of participants of the Abstract Forum. Participation in this program should be encouraged, especially in countries with high cancer prevalence and mortality.
MEDB-35. Relationship between genetic profile, histology, clinical features and long-term outcome in young children medulloblastoma (YCMB) treated with upfront high dose chemotherapy (HDCT) in Italy
Authors: Maria Luisa Garrè, Maura Massimino, Francesca Romana Buttarelli, Lorenza Gandola, Salvina Barra, Felice Giangaspero, Tobias Goschzik, Veronica Biassoni, Lorenza Pastorino, Angela Pistorio, Torsten Pietsch
Journal: Neuro-Oncology (2022)

Abstract AIMS: We report a cohort of YCMB cases homogeneously treated with HDCT in two Italian institutions, and the prognostic impact of histology and genetics retrospectively evaluated. METHODS: All YCMB (aged≤3 years) treated with upfront HDCT in the period 1998-2019 were included, reclassified according to the WHO2021 classification of CNS tumours. Mutational status ofPTCH1, SUFU, and TP53 was analysed in selected cases. Histology and genetics were correlated with survival, secondary tumours(STs), and cancer predisposition syndromes(CPSs). RESULTS: Fifty-three patients were enrolled (62.3% male), median age 2.2 years. 21 had classic(CMB), 15 desmoplastic/nodular(DMB), 11 MBEN and 6 large-cell/anaplastic(AMB/LCMB) medulloblastoma. Metastases were present in 18. Genomic pattern showed SHH-TP53wt in 29 cases, non-WNT/non-SHH in 22; 2 were SHH-TP53mut. Induction chemotherapy (VCR/HDMTX, HDVP16, VCR/HDCTX and HDCARBO) was followed by 2-3 HDCT courses; irradiation reserved to cases with metastatic disease and/or residual tumours. 22 patients never received irradiation. SHH-TP53wt cases had significantly less metastasis (p=0.002), while non-WNT/non-SHH received more often irradiation (p&amp;lt;0.0001). OS at 5, 10, and 20 yrs was 0.73, 0.70 and 0.57 respectively in the entire cohort; stable at 0.85 (at 5, 10, and 20 yrs) in SHH-TP53wt patients while 0.58, 0.51 and 0.17 in the non-WNT/non-SHH. PFS at 5, 10, 20 yrs was stable at 0.89 in SHH-TP53wt and remained 0.35 in non-WNT/non-SHH. 13/53 patients presented Gorlin Syndrome; 1 had familial MB. 16 STs were reported in 14 cases; life-threatening, irradiation-related STs mainly in non-WNT/non-SHH cases. In SHH-TP53wt benign tumours or related to CPS were reported. CONCLUSIONS: This is one of the first series of YCMB treated with HDCT without stratification for stage and histology. The long follow-up highlights the frequency/types of associated CPS and STs; the latter, in non-WNT/non-SHH, were treatment-related and life-threatening.